18F-FDG-PET in guided dose-painting with intensity modulated radiotherapy in oropharyngeal tumours: A phase I study (FiGaRO).

BACKGROUND AND PURPOSE: The FiGaRO trial assessed the feasibility and safety of using an FDG-PET-based dose-painting technique to deliver a radiotherapy (RT) boostto the FDG-avid primary tumour in patients with locally advanced high and intermediate risk oropharyngeal cancer. MATERIALS AND METHOD: Patients underwent a planning 18FDG-PET-CT scan, immobilised in the treatment position, after one cycle of induction chemotherapy. The volume of persistent FDG-avidity in the primary tumour was escalated to 71.5 Gy in30 fractions delivered using a simultaneous integrated boost Intensity Modulated RT (SIB-IMRT) technique. RT was delivered with concomitant Cisplatin following 2 cycles of induction chemotherapy. The primary outcome was the incidence of grade ≥ 3 late mucosal toxicity 12 months post-treatment, with an excess rate of >10% regarded as unacceptable. RESULTS: Twenty-nine patients were included and twenty-four were treated between 2014 and 2018, in two UK centres. Median follow-up was 36 months (range 4-56 months). Pre-defined planning target volume objectives and organ at risk dose constraints were met in all cases. There were no incidents of acute grade 4 toxicity. There were 4 cases of grade ≥ 3 mucosal toxicity at 12 months post-treatment (19.1%). There were no cases of persistent mucosal ulceration at 12 months. Overall survival at 3-years was 87.5%, 92.9% for intermediate and 70.0% for high risk patients. CONCLUSION: Late toxicity rates, although higher than anticipated, are comparable to contemporary published data for standard dose chemo-IMRT. Results suggest improved 3y survival rates for high risk patients. This approach merits further investigation. ClinicalTrials.gov Identifier: NCT02953197.

Study of out-of-field dose in photon radiotherapy: A commercial treatment planning system versus measurements and Monte Carlo simulations.

PURPOSE: An accurate assessment of out-of-field dose is necessary to estimate the risk of second cancer after radiotherapy and the damage to the organs at risk surrounding the planning target volume. Although treatment planning systems (TPSs) calculate dose distributions outside the treatment field, little is known about the accuracy of these calculations. The aim of this work is to thoroughly compare the out-of-field dose distributions given by two algorithms implemented in the Monaco TPS, with measurements and full Monte Carlo simulations. METHODS: Out-of-field dose distributions predicted by the collapsed cone convolution (CCC) and Monte Carlo (MCMonaco ) algorithms, built into the commercially available Monaco version 5.11 TPS, are compared with measurements carried out on an Elekta Axesse linear accelerator. For the measurements, ion chambers, thermoluminescent dosimeters, and EBT3 film are used. The BEAMnrc code, built on the EGSnrc system, is used to create a model of the Elekta Axesse with the Agility collimation system, and the space phase file generated is scored by DOSXYZnrc to generate the dose distributions (MCEGSnrc ). Three different irradiation scenarios are considered: (a) a 10 × 10 cm2 field, (b) an IMRT prostate plan, and (c) a three-field lung plan. Monaco's calculations, experimental measurements, and Monte Carlo simulations are carried out in water and/or in an ICRP110 phantom. RESULTS: For the 10 × 10 cm2 field case, CCC underestimated the dose, compared to ion chamber measurements, by 13% (differences relative to the algorithm) on average between the 5% and the ≈2% isodoses. MCMonaco underestimated the dose only from approximately the 2% isodose for this case. Qualitatively similar results were observed for the studied IMRT case when compared to film dosimetry. For the three-field lung plan, dose underestimations of up to ≈90% for MCMonaco and ≈60% for CCC, relative to MCEGSnrc simulations, were observed in mean dose to organs located beyond the 2% isodose. CONCLUSIONS: This work shows that Monaco underestimates out-of-field doses in almost all the cases considered. Thus, it does not describe dose distribution beyond the border of the field accurately. This is in agreement with previously published works reporting similar results for other TPSs. Analytical models for out-of-field dose assessment, MC simulations or experimental measurements may be an adequate alternative for this purpose.

External photon radiation treatment for prostate cancer: Uncomplicated and cancer-free control probability assessment of 36 plans.

PURPOSE: To perform a systematic and thorough assessment, using the Uncomplicated and Cancer-Free Control Probability (UCFCP) function, of a broad range of photon prostate cancer RT treatments, on the same scenario (a unique pelvic CT set). UCFCP considers, together with the probabilities of local tumour control (TCP) and deterministic (late) sequelae (NTCP), the second primary cancer risk (SPCR) due to photon and neutron peripheral doses. METHODS AND MATERIALS: Thirty-six radiotherapy plans were produced for the same CT. 6, 10, 15 and 18 MV 3DCRT, IMRT and VMAT (77.4 Gy in 43 fractions) and 6 and 10 MV SBRT (36.25 Gy in 5 fractions with flattened and FFF beams) for Elekta, Siemens and Varian Linacs plans were included. DVH and peripheral organ dosimetry were used to compute TCP, NTCP, and SPCR (the competition and LNT models) for further plan ranking. RESULTS: Biological models (and parameters) used predicted an outcome which is in agreement with epidemiological findings. SBRT plans showed the lowest SPCR and a below average NTCPrectal. High energy plans did not rank worse than the low energy ones. Intensity modulated plans were ranked above the 3D conformal techniques. CONCLUSIONS: According to UCFCP, the best plans were the10 MV SBRTs. SPCR rates were low and did not show a substantial impact on plan ranking. High energy intensity-modulated plans did not increase in excess the average of SPCR. Even more, they ranked among the best, provided that MU were efficiently managed.

10-MV SBRT FFF IRRADIATION TECHNIQUE IS ASSOCIATED TO THE LOWEST PERIPHERAL DOSE: THE OUTCOME OF 142 TREATMENT PLANS FOR THE 10 MOST COMMON TUMOUR LOCATIONS.

There is a growing interest in the combined use of Stereotactic Body Radiation Therapy (SBRT) with Flattening Filter Free (FFF) due to the high local control rates and reduced treatment times, compared to conventionally fractionated treatments. It has been suggested that they may also provide a better radiation protection to radiotherapy patients as a consequence of the expected decrease in peripheral doses. This work aims to determine this reduction in unattended out-of-field regions, where no CT information is available but an important percentage of second primary cancers occur. For that purpose, ten different cases suitable for SBRT were chosen. Thus, 142 different treatment plans including SBRT, as well as 3D-CRT, IMRT and VMAT (with standard fractionation) in low and high energies for Varian (FF and FFF), Siemens and Elekta machines were created. Then, photon and neutron peripheral dose in 14 organs were assessed and compared using two analytical models. For the prostate case, uncomplicated and cancer free control probability estimation was also carried out. As a general behavior, SBRT plans led to the lowest peripheral doses followed by 3D-CRT, VMAT and IMRT, in this order. Unflattened beams proved to be the most effective in reducing peripheral doses, especially for 10 MV. The obtained results suggest that FFF beams for SBRT with 10 MV represent the best compromise between dose delivery efficiency and peripheral dose reduction.

Peripheral equivalent neutron dose model implementation for radiotherapy patients.

PURPOSE: Neutron peripheral contamination in high-energy radiotherapy implies an increase of secondary radiation-induced cancer risk. Although peripheral neutron dose (PND) has been evaluated in organs, few studies have been performed regarding patient size. This work aims to improve an existing methodology for adult patient PND estimations to generalize it to young and children, for its implementation in treatment planning systems (TPS). METHODS: As a first step, we aimed to generalize the previous model to be usable with any thermal neutron detector. Then, taking into account total neutron spectra and dose-to-point thermal neutron fluence measurements for three phantom sizes (adult, teen and child) and two common treatment locations (H&N and abdomen), the new model was proposed. It represents an upgraded parameterization and extension of the existing one, including patient anatomy. Finally, comparison between estimations and measurements, as well as validation against the original model, was carried out for 510 measured patients. RESULTS: Concordance found between experimental and theoretical estimations makes us confident about later implementation in treatment planning systems. Comparison among the previous and upgraded models shows no significant differences for the adult case. However, an important underestimation (34.1% on average) can be observed regarding child case for the original one. CONCLUSIONS: An improved generalization of an existing PND model, considering patient anatomy has been validated and used in real patients. The final methodology is easily implementable in clinical routine and TPS thanks to the ready availability of input parameters (patient height and weight, high-energy MU and facility characterization).

Neutron measurements in radiotherapy: A method to correct neutron sensitive devices for parasitic photon response.

One of the major causes of secondary malignancies after radiotherapy treatments are peripheral doses, known to increase for some newer techniques (such as IMRT or VMAT). For accelerators operating above 10MV, neutrons can represent important contribution to peripheral doses. This neutron contamination can be measured using different passive or active techniques, available in the literature. As far as active (or direct-reading) procedures are concerned, a major issue is represented by their parasitic photon sensitivity, which can significantly affect the measurement when the point of test is located near to the field-edge. This work proposes a simple method to estimate the unwanted photon contribution to these neutrons. As a relevant case study, the use of a recently neutron sensor for "in-phantom" measurements in high-energy machines was considered. The method, called "Dual Energy Photon Subtraction" (DEPS), requires pairs of measurements performed for the same treatment, in low-energy (6MV) and high energy (e.g. 15MV) fields. It assumes that the peripheral photon dose (PPD) at a fixed point in a phantom, normalized to the unit photon dose at the isocenter, does not depend on the treatment energy. Measurements with ionization chamber and Monte Carlo simulations were used to evaluate the validity of this hypothesis. DEPS method was compared to already published correction methods, such as the use of neutron absorber materials. In addition to its simplicity, an advantage of DEPs procedure is that it can be applied to any radiotherapy machine.

Improving the neutron-to-photon discrimination capability of detectors used for neutron dosimetry in high energy photon beam radiotherapy.

The increasing interest of the medical community to radioinduced second malignancies due to photoneutrons in patients undergoing high-energy radiotherapy, has stimulated in recent years the study of peripheral doses, including the development of some dedicated active detectors. Although these devices are designed to respond to neutrons only, their parasitic photon response is usually not identically zero and anisotropic. The impact of these facts on measurement accuracy can be important, especially in points close to the photon field-edge. A simple method to estimate the photon contribution to detector readings is to cover it with a thermal neutron absorber with reduced secondary photon emission, such as a borated rubber. This technique was applied to the TNRD (Thermal Neutron Rate Detector), recently validated for thermal neutron measurements in high-energy photon radiotherapy. The positive results, together with the accessibility of the method, encourage its application to other detectors and different clinical scenarios.

Using a Tandem Pelletron accelerator to produce a thermal neutron beam for detector testing purposes.

Active thermal neutron detectors are used in a wide range of measuring devices in medicine, industry and research. For many applications, the long-term stability of these devices is crucial, so that very well controlled neutron fields are needed to perform calibrations and repeatability tests. A way to achieve such reference neutron fields, relying on a 3 MV Tandem Pelletron accelerator available at the CNA (Seville, Spain), is reported here. This paper shows thermal neutron field production and reproducibility characteristics over few days.

Commissioning the neutron production of a Linac: development of a simple tool for second cancer risk estimation.

PURPOSE: Knowing the contribution of neutron to collateral effects in treatments is both a complex and a mandatory task. This work aims to present an operative procedure for neutron estimates in any facility using a neutron digital detector. METHODS: The authors' previous work established a linear relationship between the total second cancer risk due to neutrons (TR(n)) and the number of MU of the treatment. Given that the digital detector also presents linearity with MU, its response can be used to determine the TR(n) per unit MU, denoted as m, normally associated to a generic Linac model and radiotherapy facility. Thus, from the number of MU of each patient treatment, the associated risk can be estimated. The feasibility of the procedure was tested by applying it in eight facilities; patients were evaluated as well. RESULTS: From the reading of the detector under selected irradiation conditions, m values were obtained for different machines, ranging from 0.25 × 10(-4)% per MU for an Elekta Axesse at 10 MV to 6.5 × 10(-4)% per MU for a Varian Clinac at 18 MV. Using these values, TR(n) of patients was estimated in each facility and compared to that from the individual evaluation. Differences were within the range of uncertainty of the authors' methodology of equivalent dose and risk estimations. CONCLUSIONS: The procedure presented here allows an easy estimation of the second cancer risk due to neutrons for any patient, given the number of MU of the treatment. It will enable the consideration of this information when selecting the optimal treatment for a patient by its implementation in the treatment planning system.

A new online detector for estimation of peripheral neutron equivalent dose in organ.

PURPOSE: Peripheral dose in radiotherapy treatments represents a potential source of secondary neoplasic processes. As in the last few years, there has been a fast-growing concern on neutron collateral effects, this work focuses on this component. A previous established methodology to estimate peripheral neutron equivalent doses relied on passive (TLD, CR39) neutron detectors exposed in-phantom, in parallel to an active [static random access memory (SRAMnd)] thermal neutron detector exposed ex-phantom. A newly miniaturized, quick, and reliable active thermal neutron detector (TNRD, Thermal Neutron Rate Detector) was validated for both procedures. This first miniaturized active system eliminates the long postprocessing, required for passive detectors, giving thermal neutron fluences in real time. METHODS: To validate TNRD for the established methodology, intrinsic characteristics, characterization of 4 facilities [to correlate monitor value (MU) with risk], and a cohort of 200 real patients (for second cancer risk estimates) were evaluated and compared with the well-established SRAMnd device. Finally, TNRD was compared to TLD pairs for 3 generic radiotherapy treatments through 16 strategic points inside an anthropomorphic phantom. RESULTS: The performed tests indicate similar linear dependence with dose for both detectors, TNRD and SRAMnd, while a slightly better reproducibility has been obtained for TNRD (1.7% vs 2.2%). Risk estimates when delivering 1000 MU are in good agreement between both detectors (mean deviation of TNRD measurements with respect to the ones of SRAMnd is 0.07 cases per 1000, with differences always smaller than 0.08 cases per 1000). As far as the in-phantom measurements are concerned, a mean deviation smaller than 1.7% was obtained. CONCLUSIONS: The results obtained indicate that direct evaluation of equivalent dose estimation in organs, both in phantom and patients, is perfectly feasible with this new detector. This will open the door to an easy implementation of specific peripheral neutron dose models for any type of treatment and facility.

Estimation of neutron-equivalent dose in organs of patients undergoing radiotherapy by the use of a novel online digital detector.

Neutron peripheral contamination in patients undergoing high-energy photon radiotherapy is considered as a risk factor for secondary cancer induction. Organ-specific neutron-equivalent dose estimation is therefore essential for a reasonable assessment of these associated risks. This work aimed to develop a method to estimate neutron-equivalent doses in multiple organs of radiotherapy patients. The method involved the convolution, at 16 reference points in an anthropomorphic phantom, of the normalized Monte Carlo neutron fluence energy spectra with the kerma and energy-dependent radiation weighting factor. This was then scaled with the total neutron fluence measured with passive detectors, at the same reference points, in order to obtain the equivalent doses in organs. The latter were correlated with the readings of a neutron digital detector located inside the treatment room during phantom irradiation. This digital detector, designed and developed by our group, integrates the thermal neutron fluence. The correlation model, applied to the digital detector readings during patient irradiation, enables the online estimation of neutron-equivalent doses in organs. The model takes into account the specific irradiation site, the field parameters (energy, field size, angle incidence, etc) and the installation (linac and bunker geometry). This method, which is suitable for routine clinical use, will help to systematically generate the dosimetric data essential for the improvement of current risk-estimation models.

SU-E-T-391: Modelling Peripheral Photon Dose in TomoTherapy Treatments.

PURPOSE: The delivery of the therapeutic radiation dose to the tumour in photon radiotherapy, also implies dose deposition in distant organs (peripheral dose) related to secondary cancers induction (Hall and Wuu, Int J Radiat Oncol Biol Phys 56:83-88, 2003). Therefore, peripheral dose estimation in MU-demanding techniques, such as Helical TomoTherapy (HT), becomes relevant. TLD measurements and Monte Carlo modelling were compared by D'Agostino (Strahlenther Onkol 187:693, 2011). The purpose of this work was to find out experimental models predicting the equivalent photon dose as a function of the distance to the isocenter for different treatment types. The prostate case is presented here. METHODS: A HT prostate plan was delivered to an anthropomorphic phantom mimicking a male adult. The phantom was made of polyethylene blocks whereas light wood was used for lungs. 16 points distributed along the phantom, covering different depths, were selected (Sánchez-Doblado IFMBE, World Congress Med Phys & Biomed Eng, 259-261, 2009). Additionally, a polyethylene sheet was inserted in the phantom to measure the off-axis dose profile at midplane depth. Measurements were carried out with standard TLD-100 pairs of dosimeters (calibrated in a 137Cs source). RESULTS: Two-exponential-terms curve fitting was carried out to model separately the scatter and leakage contribution (f=a*exp(-b*x)+c*exp(-d*x)). The former resulted predominant in the proximal region (10=x=14cm) and the latter in the distal re gion (x=14cm). Both components equate at 18cm. Scatter contribution becomes negligible for x=23cm. Points at 5cm were not used for the model as they are too close to the isocenter to be considered as peripheral dose. Model fits well experimental data (13% mean deviation). Only depths behind the build-up region could be properly modelled. CONCLUSIONS: Peripheral photon dose profiles in HT treatments have been modelled by a two-exponential-terms curve modelling separately scatter and leakage.

SU-E-T-466: TCP and NTCP: Is That All?

PURPOSE: Concerns about the secondary cancer risks associated to the peripheral neutron and photon contamination in photon modern radiotherapy (RT) techniques (e.g., Intensity Modulated RT -IMRT- or Intensity Modulated Arc Therapy -IMAT) have been widely raised. Benefits in terms of better tumor coverage have to be balanced against the drawbacks of poorer organ at risk sparing and secondary cancer risk in order to make the decision on the optimum treatment technique. The aim of this study was to develop a tool which estimates treatment success taking into consideration the neutron secondary cancer probability. METHODS: A methodology and benchmark dataset for radiotherapy real time assessment of patient neutron dose and application to a novel digital detector (DD) has been carried out (submitted to PMB, 2011). Our DD provides real time neutron equivalent dose distribution in relevant organs along the patient. This information, together with TCP and NTCP estimated from the DVH of target and organs at risks, respectively, have been built into a general biological model which allows us to evaluate the success of the treatments (Sánchez-Nieto et al., ESTRO meeting 2012). This model has been applied to make estimation of treatment success in a variety of treatment techniques (3DCRT, forward and inverse IMRT, RapidArc, Volumetric Modulated Arc Therapy and Helical Tomotherapy) to low and high energy. RESULTS: MU-demanding techniques at high energies were able to deliver treatment plans with the highest complicated-free tumour control. Nevertheless, neutron peripheral dose must be taken into consideration as the associated risk could be of the same order of magnitude than the usually considered NTCPs. CONCLUSIONS: The methodology developed to provide an online organ neutron peripheral dose can be successfully combined with biological models to make predictions on treatment success taking into consideration secondary cancer risks.

Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.

The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.

Modelos radiobiológicos: aplicación a radiocirugía / Radiobiological models: radiosurgery aplication

En este trabajo se presenta una descripción de algunos de los modelos físico-radiobiológicos más relevantes para la estimación de la probabilidad de control tumoral (TCP) y de complicación del tejido sano (NTCP).Para el caso de TCP se describe el modelo de doble exponencial (basado en la estadística de Poisson) mientras que para el NTCP los de Lyman-Kutcher-Burman y de serialidad relativa. Se discuten los rangos de validez, las aproximaciones realizadas y sensibilidad paramétrica.Se discute así mismo que, a pesar de que todos estos modelos son generales y aplicables a cualquier técnica radioterápica (incluida la radiocirugía), no ocurre así con el valor de alguno de los parámetros (e.g. dosis de toleracia), que son altamente dependientes de la dosis por fracción.Como indicación, se presentan valores de los parámetros para algunos órganos involucrados en el procedimiento radioquirúrgico (bien tomados de la escasa literatura en radiocirugía o estimados a partir de datos publicados para 2Gy/fracción). Finalmente se advierte que la actual falta de precisión en los modelos y la escasez de recopilación sistemática de datos clínicos que permitan hacer evaluaciones más precisas de los parametros, hace que los valores absolutos de TCP y NTCP deban ser empleados con mucha cautela para tomar decisiones clínicas; aunque si hay evidentes aplicaciones en estimaciones relativas en comparación de planes o evaluación de nuevas técnicas (AU)

Correlations between dose-surface histograms and the incidence of long-term rectal bleeding following conformal or conventional radiotherapy treatment of prostate cancer.

BACKGROUND AND PURPOSE: In a randomized trial, the incidence of rectal bleeding among patients treated for prostate cancer using conformal radiotherapy was significantly lower (p = 0.002) than that among those treated conventionally. Here the relationship between rectal dose distributions and incidences of bleeding is assessed. METHODS AND MATERIALS: Rectal dose-surface histograms (DSHs) have been calculated for 79 trial patients. The relationship between the DSHs and incidences of Grade 1-3 bleeding has been explored using both semiempiric and biologic (parallel) model-based approaches. RESULTS: Semiempiric analysis of the trial data suggests that it is more useful to work with DSH fractional surface areas multiplied by outlined rectal lengths than with either raw DSH fractional areas or fractional areas multiplied by absolute total outlined rectal surface area. Fitting the parallel model to length-multiplied rectal DSHs and complication data reveals the existence of a significant volume effect, the rate of Grade 1-3 bleeding falling by 1.1% (95% confidence interval [0.04, 2.2]%) for each 1% decrease in the fraction of rectal wall (outlined over an 11-cm length) receiving a dose of more than 57 Gy. CONCLUSION: The existence of this volume effect suggests that dose escalation can be achieved using conformal techniques, although the extent to which doses may be safely escalated cannot be reliably estimated from the trial data.

Individualization of dose prescription based on normal-tissue dose-volume and radiosensitivity data.

PURPOSE: The aim of this paper is to illustrate the potential gain in tumor control probability (TCP) of prostate cancer patients by individualizing the prescription dose according to both normal-tissue (N-T) dose-volume and radiosensitivity data. METHODS AND MATERIALS: Two exercises have been carried out. Firstly, patients' dose prescriptions were individualised on the basis of N-T dose-volume histograms (DVHs) alone and secondly modeling potential differences in N-T sensitivity as well. In both cases, the change in tumor control that may be achieved by individualizing patients' dose was estimated assuming that after the dose adjustments, every patient had (1) the same value of normal tissue complication probability (NTCP) (5%) and (2) NTCP equal to the average NTCP before individualization (i.e., without increasing the average NTCP). The Lyman-Kutcher-Burman NTCP model was used to predict the N-T response curves with two different sets of parameters. The first exercise, based only on individual NT DVHs (i.e., assuming all patient equally radiosensitive), was over a real population of 50 prostate cancer patients. The second exercise modeled a 10,000-prostate-cancer patient population with varying NT dose-volume distributions and radiosensitivity (through allowing TD(50) to vary). RESULTS: A gain of more than 9% in TCP was predicted when doses were individualized based only on DVHs so that every patient had 5% NTCP after dose adjustments. By adding the estimate of radiosensitivity, the gain increased to more than 15%. When the individualisation was performed without increasing the mean NTCP, then the potential gain in TCP was almost 5% (for adjustment based on DVH distribution solely) increasing to 7% with the additional consideration of radiosensitivity. CONCLUSIONS: There is a potential gain (increase in local tumor control) from dose individualisation strategies based on both N-T dose-volume data and radiosensitivity (assuming that this is available). Dose prescription individualization based only on dose-volume data can be exploited provided that reliable N-T response models are available. There will be additional gains if some estimate of N-T radiosensitivity is available to allow further patient stratification, identification of patients with high radiosensitivity being particularly important.

BIOPLAN: software for the biological evaluation of. Radiotherapy treatment plans.

Distributions of absorbed dose do not provide information on the biological response of tissues (either tumor or organs at risk [OAR]) to irradiation. BIOPLAN (BiOlogical evaluation of PLANs) has been conceived and developed as a PC-based user-friendly software that allows the user to evaluate a treatment plan from the (more objective) point of view of the biological response of the irradiated tissues, and at the same time, provides flexibility in the use of models and parameters. It requires information on dose-volume histograms (DVHs) and can accept a number of different formats (including DVH files from commercial treatment planning systems). BIOPLAN provides a variety of tools, such as tumor control probability (TCP) calculations (using the Poisson model), normal tissue complication probability (NTCP) calculations (using either the Lyman-Kutcher-Burman or the relative seriality models), the ATCP method, DVH subtraction, plots of NTCP/TCP as a function of prescription dose, tumor and OAR dose statistics, equivalent uniform dose (EUD), individualized dose prescription, and parametric sensitivity analysis of the TCP/NTCP models employed.

The delta-TCP concept: a clinically useful measure of tumor control probability.

PURPOSE: The aim of this article is to provide a quantitative tool to evaluate the influence of the different dose regions in a non-uniformly irradiated tumour upon the probability of controlling that tumor. METHODS AND MATERIALS: First, a method to generate a distribution of the probability of controlling the cells in a voxel (VCP) is explored and found not to be useful. Second, we introduce the concept of delta-TCP, which represents the gain or loss in the overall TCP as a result of each particular bin in a DVH not receiving the prescribed dose (the same concept is applicable to dose cubes or to a fraction of the bin). The delta-TCP method presented here is based on the Poisson TCP model, but any other model could also be used. Third, using this tool, with parameters appropriate to Stage C prostate tumors, the consequences of "cold" and "hot" dose regions have been explored. RESULTS: We show that TCP is affected by the minimum dose, even if it is delivered to a very small volume (20% dose deficit to 5% of the volume makes the TCP decrease by 18%), and that a hot region may be "wasted" unless the boost is to the bulk of the volume. An example of the application of the delta-TCP concept to a prostate radiotherapy plan is also given. CONCLUSION: The delta-TCP distribution adds more objective information to the original DVH by enabling the clinician or planner to directly evaluate the effects of a non-uniform dose distribution on local control.